Improving genetic diagnosis in Mendelian disease with transcriptome sequencing

Author:

Cummings Beryl B.123ORCID,Marshall Jamie L.12,Tukiainen Taru12ORCID,Lek Monkol1245,Donkervoort Sandra6,Foley A. Reghan6,Bolduc Veronique6ORCID,Waddell Leigh B.45,Sandaradura Sarah A.45,O’Grady Gina L.45,Estrella Elicia7ORCID,Reddy Hemakumar M.8ORCID,Zhao Fengmei12ORCID,Weisburd Ben12,Karczewski Konrad J.12ORCID,O’Donnell-Luria Anne H.12ORCID,Birnbaum Daniel12,Sarkozy Anna9ORCID,Hu Ying6ORCID,Gonorazky Hernan10ORCID,Claeys Kristl11,Joshi Himanshu5ORCID,Bournazos Adam45ORCID,Oates Emily C.45ORCID,Ghaoui Roula45,Davis Mark R.12ORCID,Laing Nigel G.1213ORCID,Topf Ana14,Kang Peter B.78,Beggs Alan H.7ORCID,North Kathryn N.15ORCID,Straub Volker14ORCID,Dowling James J.10,Muntoni Francesco9,Clarke Nigel F.45,Cooper Sandra T.45ORCID,Bönnemann Carsten G.6ORCID,MacArthur Daniel G.12ORCID,

Affiliation:

1. Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.

2. Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.

3. Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA.

4. School of Paediatrics and Child Health, University of Sydney, Sydney, New South Wales 2006, Australia.

5. Institute for Neuroscience and Muscle Research, Kids Research Institute, The Children’s Hospital at Westmead, Sydney, New South Wales 2145, Australia.

6. Neuromuscular and Neurogenetic Disorders of Childhood Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.

7. Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

8. Division of Pediatric Neurology, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610, USA.

9. Dubowitz Neuromuscular Centre, University College London Institute of Child Health, London WC1N 1EH, U.K.

10. Division of Neurology, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.

11. Department of Neurology, University Hospitals Leuven and University of Leuven (Katholieke Universiteit Leuven), Leuven 3000, Belgium.

12. Department of Diagnostic Genomics, PathWest Laboratory Medicine, Perth, Western Australia 6009, Australia.

13. Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Western Australia 6009, Australia.

14. John Walton Muscular Dystrophy Research Centre, MRC (Medical Research Council) Centre for Neuromuscular Diseases, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, U.K.

15. Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, Melbourne, Victoria 3052, Australia.

Abstract

Transcriptome sequencing improves the diagnostic rate for Mendelian disease in patients for whom genetic analysis has not returned a diagnosis.

Funder

Broad Institute

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

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